Related papers: Modelling chromosome-wide target search
Several processes in the cell, such as gene regulation, start when key proteins recognise and bind to short DNA sequences. However, as these sequences can be hundreds of million times shorter than the genome, they are hard to find by simple…
Strong experimental and theoretical evidence shows that transcription factors and other specific DNA-binding proteins find their sites using a two-mode search: alternating between 3D diffusion through the cell and 1D sliding along the DNA.…
The most common gene regulation mechanism is when a protein binds to a regulatory sequence to change RNA transcription. However, these sequences are short relative to the genome length, so finding them poses a challenging search problem.…
Under dilute in vitro conditions transcription factors rapidly locate their target sequence on DNA by using the facilitated diffusion mechanism. However, whether this strategy of alternating between three-dimensional bulk diffusion and…
Problems of search and recognition appear over different scales in biological systems. In this review we focus on the challenges posed by interactions between proteins, in particular transcription factors, and DNA and possible mechanisms…
The model of facilitated diffusion describes how DNA-binding proteins, such as transcription factors (TFs), find their chromosomal targets by combining 3D diffusion through the cytoplasm and 1D sliding along nonspecific DNA sequences. The…
We develop revised theoretical ideas on the mechanism by which the transcription factor proteins locate their specific binding sites on DNA faster than the three-dimensional (3D) diffusion controlled rate limit. We demonstrate that the…
Transcription factor proteins bind specific DNA sequences to control the expression of genes. They contain DNA binding domains which belong to several super-families, each with a specific mechanism of DNA binding. The total number of…
Response time and transcription level are vital parameters of gene regulation. They depend on how fast transcription factors (TFs) find and how efficient they occupy their specific target sites. It is well known that target site search is…
Surviving in a diverse environment requires corresponding organism responses. At the cellular level, such adjustment relies on the transcription factors (TFs) which must rapidly find their target sequences amidst a vast amount of…
Gene regulation is one of the most important fundamental biological processes in living cells. It involves multiple protein molecules that locate specific sites on DNA and assemble gene initiation or gene repression multi-molecular…
Genomic expression depends critically both on the ability of regulatory proteins to locate specific target sites on a DNA within seconds and on the formation of long lived (many minutes) complexes between these proteins and the DNA.…
To ensure fast gene activation, Transcription Factors (TF) use a mechanism known as facilitated diffusion to find their DNA promoter site. Here we analyze such a process where a TF alternates between 3D and 1D diffusion. In the latter (TF…
DNA is subject to large deformations in a wide range of biological processes. Two key examples illustrate how such deformations influence the readout of the genetic information: the sequestering of eukaryotic genes by nucleosomes, and DNA…
We study a protein-DNA target search model with explicit DNA dynamics applicable to in vitro experiments. We show that the DNA dynamics plays a crucial role for the effectiveness of protein "jumps" between sites distant along the DNA…
Recent experiments show that transcription factors (TFs) indeed use the facilitated diffusion mechanism to locate their target sequences on DNA in living bacteria cells: TFs alternate between sliding motion along DNA and relocation events…
Transcription factor (TF) molecules translocate by facilitated diffusion (a combination of 3D diffusion around and 1D random walk on the DNA). Despite the attention this mechanism received in the last 40 years, only a few studies…
Some proteins can find their targets on DNA faster than by pure diffusion in the three-dimensional cytoplasm, through the process of facilitated diffusion: They can loosely bind to DNA and temporarily slide along it, thus being guided by…
We study a model for a protein searching for a target, using facilitated diffusion, on a DNA molecule confined in a finite volume. The model includes three distinct pathways for facilitated diffusion: (a) sliding - in which the protein…
Current models for the folding of the human genome see a hierarchy stretching down from chromosome territories, through A/B compartments and TADs (topologically-associating domains), to contact domains stabilized by cohesin and CTCF.…